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Anna Rydén



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    Proffered Paper session I (ID 57)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/10/2019, 16:30 - 18:15, Room C
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      LBA2 - Patient-reported outcomes (PROs) with durvalumab by PD-L1 expression in unresectable, stage III NSCLC (PACIFIC) (ID 308)

      16:30 - 18:15  |  Author(s): Anna Rydén

      • Abstract
      • Presentation
      • Slides

      Background

      In the ph 3 PACIFIC study of Stage III NSCLC pts without progression after cCRT, PFS and OS were significantly improved with durva vs. pbo, with no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs.

      a9ded1e5ce5d75814730bb4caaf49419 Background

      In the phase 3 PACIFIC study of unresectable, Stage III NSCLC pts without progression after platinum-based concurrent chemoradiotherapy (cCRT), the primary endpoints PFS and OS were significantly improved with durvalumab versus placebo with similar safety and no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs to better understand the benefit/risk profile of durvalumab across all PD-L1 subgroups.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      After ≥2 cCRT cycles, pts were randomised (2:1) to durva 10 mg/kg or pbo IV q2w up to 12 mo. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25% or unknown) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from BL analysed by a mixed model for repeated measures, HRs for time to deterioration (TTD) by a stratified Cox proportional-hazards model, and ORs for improvement rates by logistic regression.

      20c51b5f4e9aeb5334c90ff072e6f928 Methods

      After cCRT with ≥2 chemotherapy cycles, pts were randomised (2:1) to durvalumab 10 mg/kg or placebo IV q2w up to 12 months. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25%) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from baseline (BL) analysed by a mixed model for repeated measures, hazard ratios (HRs) for time to deterioration (TTD) by a Cox proportional-hazards model, and odd ratios (ORs) for improvement rates by logistic regression.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Of 713 pts, 63% had known PD-L1 status. Compliance was high (>80% at Wk 48) across all five PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, and unknown). Most PROs remained stable; however, similar to the ITT population, clinically relevant improvements from BL to Wk 48 were observed for dysphagia and alopecia across most subgroups (4/5 and 5/5, respectively) for durva (mean changes 10.1−20.9 and 15.5−26.9) and all for pbo (10.4−19.4 and 15.8−31.3); plus improvements with pbo for TC ≥25% (12.5 for chest pain and constipation) and TC <25% (10.0 for appetite loss and arm/shoulder pain). Across most subgroups, there were no TTD differences, except those favouring durva: for TC ≥25%, chest pain (HR=0.57), physical functioning (0.60), emotional functioning (0.47), pain (0.56), and haemoptysis (0.42); and, similar to ITT, for TC ≥25%, <25%, ≥1% and <1%, ‘other pain’ (0.60, 0.57, 0.67 and 0.39, respectively). Improvement rates were also similar, except as follows, favouring durva: for TC ≥25%, role functioning (OR=2.84) and, similar to ITT, appetite loss (4.33); for TC ≥1%, diarrhoea (4.50) and haemoptysis (19.34); and, for TC<1%, ‘other pain’ (7.25); for TC<25%, the rate favoured pbo for cough (0.51).

      fd69c5cf902969e6fb71d043085ddee6 Results

      Of 713 pts, 63% had known PD-L1 status. Similar to the intent-to-treat (ITT) population, most PROs remained stable over time from BL across the PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, or unknown), with no clinically meaningful (CM) differences (≥10 points) for durvalumab compared to placebo. However, similar to the ITT population, CM improvements (decreases ≥10 points) from BL to Week 48 were observed for dysphagia and alopecia across most PD-L1 subgroups for both durvalumab (mean changes 8.1 [not CM]−20.9 and 15.5 − 26.9, respectively) and placebo (mean changes 10.4 − 19.4 and 15.8 − 31.3). Pre-specified and post hoc TTD analyses of PROs by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping HR and 95% CIs. Similarly, PRO improvement rates by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping OR and 95% CIs.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Similar to the ITT population, there were minimal between-Tx differences in PROs based on PD-L1 expression, supporting use of the PACIFIC regimen (durvalumab after cCRT) in all comers.

      b651e8a99c4375feb982b7c2cad376e9 Conclusions

      There were no CM differences in PROs between treatment arms across various PD-L1 subgroups. Results were generally consistent with those in the ITT population, suggesting that PD-L1 expression did not influence PROs in this study.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02125461

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, PhD, of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      M.C. Garassino: Personal fees: AstraZeneca, Roche, BMS, MSD. L. Paz-Ares: Advisory fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merck, Boehringer Ingelheim, outside the conduct of the study. C. Faivre-Finn: Research funding: AstraZeneca, MSD, outside the conduct of the study. A. Spira: Consultant fees, institutional research support: AstraZeneca, outside the conduct of the study. D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the conduct of the study. M. Ozguroglu: Consultant fees: Astellas; Honoraria: Janssen, outside the conduct of the study. A. Rydén, P.A. Dennis: Employment, stock: AstraZeneca. Y. Zhang, C. O’Brien: Employment, stock: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.

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